A mass spectrometer is an analytical tool for determining the mass of sample ions based on its mass to charge ratio (m/z). A sample solution may be ionized by inducing either the loss or gain of a charge before introducing the resulting ions into a mass analyzer. The formed ions are separated afterwards according to their relative mass to charge ratios followed by detection to provide a resulting mass spectrum.
A variety of ionization techniques are available today that may be selected based upon a particular application. Each ionization technique can be specifically chosen for its unique ability to provide certain results depending upon device sensitivities and mass ranges that may be required. Electrospray ionization (ESI) for example is a method often used for analysis of molecules such as peptides, proteins and carbohydrates. A fine spray of highly charged droplets is formed in the presence of an electrical field and directed to an mass analyzer. Because a solution can be continuously introduced for analysis, ESI is particularly suitable for and often interfaced with sample preparation techniques such as liquid chromatography (LC) and capillary electrophoresis (CE). ESI is further interfaced with a variety of mass analyzers such as time-of-flight or quadrupole ion trap mass analyzers. While most mass analyzers achieve the same basic result of ion separation, each can accomplish this goal differently in that some may separate ions based on space or positioning, while others may separate ions based on time. For example, an ion trap mass analyzer traps ion species of a selected m/z ratio within a radio frequency (RF) quadrupole field. The quadrupole electric field formed inside an ion trap mass spectrometer is accomplished by applying an RF voltage so as to capture and accumulate ions before they are selectively ejected to a detector afterwards. Accumulation of ions for extended period of time enhances the signal-to-noise ratio of species delivered to an ion trap mass spectrometer by continuous flow separation techniques such as CE which may not be accomplished with other types of mass spectrometers.
The sensitivity and performance of trapping mass analyzers is known to diminish when there is a large abundance of undesired ion species within a mixture which can be referred to as background ions. The analysis of complex mixtures frequently involve the presence of only small amounts of important components amidst an abundance of relatively irrelevant ions. In order to fully recognize the potential of mass spectrometers as powerful analytical tools for biological applications, they must perform qualitative and quantitative molecular analysis of complex mixtures where the relative abundances of discernable components can vary by many orders of magnitude. For example, a major goal of research in the field of proteomics or biomarker pattern discovery calls for the highly selective analysis of many important classes of proteins which are often present in relatively low concentrations. The possible range of peptide or protein concentrations in proteomic measurements can be many orders of magnitude less in comparison to other mixture components that are not of interest. When interfaced with CE separation techniques in particular, the total number of ion species eluted and the complexity of the overall mixture itself can be significant while the relative abundance of components of interest is extremely limited. The elution of highly abundant peptides can restrict the detection of less abundant peptides eluting at or near the same time since the dynamic range of mass spectrometers can be relatively limited. In other words, the detection sensitivity for ions of interest deteriorates when there is a large amount of background ions. There is a need for solutions that enhance the dynamic range and sensitivity of ion trap mass spectrometers for analysis of complex mixtures with components having varying abundances which can differ by many orders of magnitude.